1. Investigación

The lens proteome undergoes dramatic composition changes during development and maturation. A defective developmental process leads to congenital cataracts that account for about 30% of cases of childhood blindness. Gene mutations are associated with approximately 50% of early-onset forms of lens opacity, with the remainder being of unknown etiology. To gain a better understanding of cataractogenesis, we utilized a transgenic mouse model expressing a mutant ubiquitin protein in the lens (K6W-Ub) that recapitulates most of the early pathological changes seen in human congenital cataracts. We performed mass spectrometry-based tandem-mass-tag quantitative proteomics in E15, P1, and P30 control or K6W-Ub lenses. Our analysis identified targets that are required for early normal differentiation steps and altered in cataractous lenses, particularly metabolic pathways involving glutathione and amino acids. Computational molecular phenotyping revealed that glutathione and taurine were spatially altered in the K6W-Ub cataractous lens. High-performance liquid chromatography revealed that both taurine and the ratio of reduced glutathione to oxidized glutathione, two indicators of redox status, were differentially compromised in lens biology. In sum, our research documents that dynamic proteome changes in a mouse model of congenital cataracts impact redox biology in lens. Our findings shed light on the molecular mechanisms associated with congenital cataracts and point out that unbalanced redox status due to reduced levels of taurine and glutathione, metabolites already linked to age-related cataract, could be a major underlying mechanism behind lens opacities that appear early in life.

A cataract is defined as opacity of the crystalline lens. It is currently one of the most prevalent ocular pathologies and is generally associated with aging. The most common treatment for cataracts is surgery. Cataract surgery is a quick and painless process, is very effective, and has few risks. The operation consists of removing the opacified lens and replacing it with an intraocular lens. The most common intraocular lens removal procedure that is currently used is phacoemulsification. The energy applied in this process is generated by ultrasonic waves, which are mechanical waves with a frequency higher than 20 kHz. A great deal of research on the different ways to perform the stages of this surgical procedure and the analysis of the possible side effects of the operation has been published, but there is little information on the technical characteristics, the intensities applied, and the use of ultrasound-emitting (U/S) equipment for cataract removal. More studies on the method and depth of absorption of ultrasonic waves in our visual system when performing the phacoemulsification procedure are needed. It would be advisable for health authorities and medical professionals to develop guidelines for the handling and use of ultrasonic wave-emitting equipment, such as those that exist for ultrasound and physiotherapy. This could help us to reduce undesirable effects after the operation.